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Overexpression of cyclooxygenase-2 in urothelial carcinoma in conjunction with tumor-associated-macrophage infiltration, hypoxia-inducible factor-1α expression, and tumor angiogenesis

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Chen W-T, Hung W-C, Kang W-Y, Huang Y-C, Su Y-C, Yang C-H, Chai C-Y. Overexpression of Cyclooxygenase-2 in Urothelial Carcinoma: in conjunction with tumor-associated-macrophage infiltration, hypoxia-inducible factor-1α expression, and tumor angiogenesis. APMIS 2009; 117:176–84.

This study examines whether the expression of cyclooxgenase-2 (COX-2) in urothelial carcinoma (UC) is associated with macrophage infiltration, hypoxia-inducible factor-1α (HIF-1α) expression and angiogenesis. We investigated the expression of COX-2 associated with HIF-1α and performed double immunohistochemical analysis of 216 UCs for COX-2 expression and the correlation with tumor-associated-macrophage (TAM) density and microvessel density (MVD) in situ. A high expression of COX-2 was positively correlated with tumor invasiveness, histologic grade and HIF-1α expression in UC (p<0.0001, p=0.003, p<0.0001, respectively). Quantification of double staining of COX-2/CD34 and COX-2/CD68 showed that a higher MVD and TAM density was found in COX-2 high-expression than in COX-2 low-expression tumor fields (p<0.0001). Adjacent to the principal of COX-2 expression areas, MVD value and TAM density were significantly increased in HIF-1α high-expression specimens compared with HIF-1α low-expression ones (p<0.0001). Interestingly, our data revealed that high COX-2 expression (p=0.002), high HIF-1α expression (p<0.0001) and TAM density (p<0.0001) were all associated with high MVD value. Our results suggest that COX-2 may produce a cooperative effect in promoting tumor progression and may be involved in the process of angiogenesis through increasing TAM infiltration or HIF-1α regulation by hypoxia.

Keywords: Urothelial carcinoma; hypoxia-inducible factor-1α; immunohistochemistry; microvessel density; tumor-associated-macrophage

Document Type: Research Article


Affiliations: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung;

Publication date: March 1, 2009

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